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Therapeutic Alternatives for the Hirsute Patient

Pittaway DE et al., 1982

Comparison between tamoxifen and clomiphene for induction of ovulation

Messinis IE et al., 1982·Acta Obstet Gynecol Scand

The effectiveness of tamoxifen and clomiphene in inducing ovulation was compared in 46 women with anovulatory infertility. All the women were given both the drugs in an alternate way. If one cycle was treated by tamoxifen the next was treated by clomiphene and vice versa. Forty-one out of the 46 women (89.1%) ovulated at least once during the study. Similar ovulation rates were achieved by tamoxifen (56.2%) and clomiphene (62.9%). The lengths of the ovulatory cycles and their luteal phases and the mid-luteal phase serum progesterone levels did not differ significantly between the two compounds. Nor did the occurrence of luteal phase defects during the tamoxifen and clomiphene treatment cycles differ. Thirty-seven of the 46 women (80.4%) responded similarly to both drugs. Thus, tamoxifen is just as effective as clomiphene in inducing ovulation in women with anovulation.

Natural family planning: ovulation method after Billings (author's transl)

Meier-Vismara E et al., 1982·Geburtshilfe Frauenheilkd

During the last decade, the World Health Organization has paid increasing attention to some reliable methods of birth control based on periodic abstinence. There are 2 main methods of natural family planning--the Sympto-Thermal method and the Billings Ovulation method. The latter is explained in this paper. Its scientific basis, use, effectiveness, and importance as a birth control method as well as for understanding certain types of infertility are discussed. (author's)

Clues from Research into Cross-Species Fertilization

Thadani VM, 1982·Journal of Experimental Zoology

Dialysis encephalopathy and osteomalacic bone disease: a case-controlled study

J C Prior et al., 1982·Am J Med

Nine patients on long-term hemodialysis with dialysis encephalopathy were studied, with sex matched control subjects for eight of the patients. Each patient with dialysis encephalopathy and control subject were contemporaries in a similar dialysis environment. Rib and other fractures were found in excess in the patients with dialysis encephalopathy (p less than 0.005 and p less than 0.01). These patients had less radiographic hyperparathyroid bone disease, and no more osteopenia as measured by metacarpal thickness than did their control counterparts. Severe osteomalacia was documented by bone biopsy in four of te patients. In a retrospective review of clinical, biochemical and pharmacologic differences, the patients with dialysis encephalopathy were significantly older at the start of dialysis (45.6 years versus 38.6 years, p less than 0.02) and had higher mean concentrations of blood urea nitrogen (BUN) and lower serum hemoglobin in the first year of dialysis than the control subjects. Blood pressure weight, creatinine, calcium, phosphate, alkaline phosphatase and a number of transfusions did not differ significantly. There was no difference in prescribed vitamin D and elemental aluminum in phosphate binders. This study demonstrates that patients with dialysis encephalopathy had more rib fractures without more parathyroid or osteopenic bone disease than did the control subjects and suggests that the etiology of dialysis encephalopathy and osteomalacia is multifactorial.

Endocrine, structural, and functional changes in the uterus during premature labor

Garfield RE et al., 1982·Am J Obstet Gynecol

Rats which were subjected to ovariectomy on day 18 of pregnancy and were treated with 17 beta-estradiol underwent delivery prematurely at 0900 +/- 1.9 hours on the morning of day 18. All animals had in plasma and uterine tissue a precipitate and highly significant progesterone withdrawal and a corresponding significant increase in prostaglandin F and prostaglandin F metabolite. Progesterone replacement therapy given to a second group of castrated animals prevented progesterone withdrawal and premature labor, because the hormonal profile in plasma and uterine tissue of these animals was identical with that of the intact pregnant vehicle controls. Electron microscopy of longitudinal and circular myometrial layers showed a precipitate and highly significant increase in the number, size, and area of gap junctions in the uteri of the group undergoing premature delivery. In the uteri of the progesterone-treated and vehicle control groups (both intact pregnant), gap junctions were conspicuously scarce. Thus the extensive regulatory imbalance, provoked by progesterone withdrawal, induced a significant increase in myometrial gap junctions. This structural change established contacts between individual myometrial cell which could transform the multibillion cell community of the uterus into a syncytium, to generate low-resistance pathways to the flow of current and thus promote the propagation of trains of electrical discharge in support of labor.

The Beginnings of Human Life

Hilgers TW, 1982

Reproductive performance of women with uterine anomalies. An evaluation of 182 cases

Heinonen PK et al., 1982·Acta Obstet Gynecol Scand

A total of 182 women with uterine anomalies were observed over a period of 18 years. In all, 126 women had 265 pregnancies, fetal survival rate was 66%, perinatal mortality 8% and premature labors occurred in 23%. When the uterine anomalies were grouped according to degree of failure of normal and uterine development, the complete septate uteri had the best fetal survival rate (86%), complete bicornuate uteri (50%) and unicornuate (40%) poorest. Cervical cerclage was applied most in the partial bicornuate uteri (17%), where fetal before operation, 53% and after, 100%. The frequency of breech presentation was 40-50% in all groups except complete septate uteri (25%) and complete bicornuate (0%). The highest cesarean section rate (82%) was in deliveries of patients with uterus didelphys. The frequency of cesarean section among total deliveries was 53%. Metroplasty was carried out on 19 patients. The obstetric outcome improved from 10% successful pregnancies before surgery to 88% postoperatively.

The dominant ovarian follicle

Hodgen GD, 1982·Fertil Steril

Medvei VC: A History of Endocrinology

Medvei VC, 1982

Ovulation method of natural family planning

Connell-Tatum EB, 1981·Fertil Steril

Past practices of Natural Family Planning (NFP) have 1) calendar rhythm in which a constant mathematical relationship was calculated between the day of ovulation and the beginning of the succeeding menstrual period, 2) temperature rhythm in which sexual intercourse is permitted by observing that the basal body temperature rises at the time of ovulation, 3) a combination of calendar and temperature rhythm methods, 4) paper test strips which measure glucose and electrolytes in vaginal secretions, 5) electronic devices of various sorts which record changes in the potentials of the pelvic organs at the time of ovulation, and 6) recent developments in computer technology which measure a number of variables. All of these techniques depend upon the identification of the fertile and infertile periods of the menstrual cycle. More recent studies by the World Health Organization have analyzed the teaching phase of NFP and the effectiveness phase of NFP using the detection of ovulation by following changes in the quality of cervical mucus. These studies tested 869 women with varied backgrounds in 5 countries. The data support the fact that many motivated women can detect ovulation reasonably accurately by following changes in their cervical mucus (the Billings method), although teaching time and motivation are considerable. Long-term and detailed data are necessary to determine the value of these methods. The advantage of NFP is the avoidance of drugs and devices. Disadvantages are that demands are placed on the sex life of couples, and there are associations between failures and increased rates of congenital abnormalities.

Deficient cellular immunity in endometriosis

Dmowski WP et al., 1981·Am J Obstet Gynecol

Cell-mediated autoimmune responses were studied by means of in vivo and in vitro techniques in five rhesus monkeys with spontaneous endometriosis. The results were compared with similar data obtained from five normal rhesus monkeys without endometriosis. The in vivo studies included intrademal injection of autologous antigens prepared from uterine endometrium, ectopic endometrium, or peritoneum, or injection of the mitogen, phytohemagglutinin (PHA). Skin biopsies were obtained at 48 hours and evaluated under the light microscope for perivascular lymphocytic infiltration. The mean number of lymphocytes per high-power field after injection of the autologous endometrial antigen was significantly smaller in animals affected by endometriosis than in the control group. There was no significant difference in lymphocytic response to autologous peritoneal antigens between the groups. Animals of both groups responded readily to PHA with marked perivascular lymphocytic infiltration. Lymphocyte stimulation responses to the same autologous antigens or to PHA were evaluated by means of in vitro assays and micro-methods. Lymphocyte stimulation response to autologous endometrial antigens in the group with endometriosis was significantly less than in the control group. There was no significant difference in response to the peritoneal antigens between the groups, and the response to PHA was marked in all animals of both groups. The results of this study indicate that rhesus monkeys with spontaneous endometriosis have an altered cellular immune response to autologous antigens. Although the animals were immunologically competent, as judged by responses to PHA, both in vivo and in vitro studies indicated a decrease in the cell-mediated immune response to autologous endometrial antigens. These data suggest that endometrial cells translocated from their normal location may implant only in women with specific alteration in cell-mediated immunity. New light is thus shed on the cause of endometriosis.

Natural family planning IV. The identification of postovulatory infertility

Hilgers TW et al., 1981·Obstet Gynecol

The estimated time of ovulation (ETO) was correlated with the day of defined postovulatory infertility in 66 hormonally normal menstrual cycles from 24 subjects for each of 15 different natural family planning methodologies. Inherent weaknesses were identified in methods based upon calendar calculations or basal body temperature only. These weaknesses could be removed for the basal body temperature-only methods if symptoms, especially the peak mucus symptom, were added to the temperature records. However, the peak mucus symptom alone had the greatest precision of all methods studied. No advantage could be identified in combining the basal body temperature with the peak symptom.

Adolescent contraception

Bolton GC, 1981·Clin Obstet Gynecol

Both the medical profession and the general public are becoming more and more aware of the need for adolescent contraception and the devastating consequences of the lack of such care. It is the responsibility of family planning providers and educators to offer this type of service tailored to adolescents and their unique needs. The service must include counseling, education, provision of contraceptives, and followup medical care. To better understand adolescent contraception, it is necessary to understand adolescent sexuality, the teenage pregnancy problem, the risks of teenage pregnancy, and the unique aspects of the contraceptive methods available to teenagers. Each of these areas is reviewed. The most important developmental task of adolescence relates to sexual maturation. The child's body undergoes complex changes necessary for adult function, and the sex drive is awakened. The teenager is faced with the task of developing a sexual identity and personal values about sexual behavior. The 2 important tasks in sexual counseling of the adolescent are helping them to decide whether or not they are ready for sexual intimacy and encouraging them to assume responsibility for their sexual behavior. The consequences of adolescent sexual activity are the rise in teenage sexually transmitted diseases and the rise in teenage pregnancies. Medically, the hazards of an an overall increase in incidence of infant mortality 2-3 times that of the normal population; twice as many growth retarded infants born to teen mothers; maternal mortality 60% higher than normal; a low incidence of prenatal care early in pregnancy; and 27% of pregnancies terminated by abortion. Equally important are nonmedical consequences for the teenage parent. In general, the consequences of teen parenthood are more severe for the young mother than for the young father. Teen mothers have a suicide rate 10 times that of the general population. In discussing contraception, attention is directed to all available contraceptive methods (abstinence, sex without intercourse, natural family planning, withdrawal, condoms and vaginal spermicidal agents, diaphragm, IUDs, and abortion), but emphasis is on oral contraceptives (OCs). The popularity of OCs among adolescents is due primarily to 2 the agents are highly effective and their use is not associated directly with the act of coitus. For the physician, there are 2 concerns associated with the use of these exogenous steroids in administration might cause premature closure of the epiphyses and inhibition of full stature development; and the steroids might cause permanent hypothalamic-pituitary dysfunction. Both concerns are relatively unwarranted. The OC might be an excellent choice for the adolescent without medical contraindication, who has established regular menses, and who has intercourse on a regular or fairly frequent basis.

Fertility following bilateral ovarian wedge resection: a critical analysis of 90 consecutive cases of the polycystic ovary syndrome

Adashi EY et al., 1981·Fertil Steril

Fertility following bilateral ovarian wedge resection (BOWR) was evaluated in a retrospective cohort study of 90 consecutive cases of the polycystic ovary syndrome. Post-BOWR follow-up was available for varying time spans of up to 10 years. BOWR resulted in the resumption of menstrual cyclicity in 91.1% (82/90) of the cases. However, within this ovulatory group, 26 patients were characterized by oligo-ovulation and a significantly reduced conception rate (29.2%), as compared with that of 56 normo-ovulatory counterparts (60.3%). Although the crude overall conception rate for this series was 47.8%, the overall cumulative probability of conception at the end of follow-up as determined by life table analysis was 73%. The likelihood of conception at any given point in time was estimated by a monthly fecundability rate of 1.34%. Our findings also indicate that the probability of post-BOWR conception was unaffected by age, race, ward status, or duration of infertility. In contrast, persistent post-BOWR oligo- or anovulation and the presence of concurrent tuboperitoneal disease were reaffirmed as the most important determinants of the likelihood of post-BOWR conception. A minimum incidence of 7.8% was documented for acquired post-BOWR pelvic disease.

Sex hormone-binding globulin concentrations in women with severe premenstrual syndrome

Dalton ME, 1981·Postgrad Med J

Sex hormone binding globulin (SHBG) binding capacity was measured in 50 women with severe premenstrual syndrome and 50 age-matched controls. The binding capacity was significantly lower (P = 0.001) in the patients. This finding suggests that the levels of SHBG binding capacity could be useful in the diagnosis and may help to explain the aetiology of the premenstrual syndrome.

Do natural methods for fertility regulation increase the risks of genetic errors?

Serra A, 1981·Bull Nat Fam Plan Counc Vic

Genetic errors of many kinds are connected with the reproductive processes and are favored by a nunber of largely uncontrollable, endogenous, and/or exogenous factors. For a long time human beings have taken into their own hands the control of this process. The regulation of fertility is clearly a forceful request to any family, to any community, were it only to lower the level of the consequences of genetic errors. In connection with this request, and in the context of the Congress for the Family of Africa and Europe (Catholic University, January 1981), 1 question must still be raised and possibly answered. do or can the so called "natural methods" for the regulation of fertility increase the risks of genetic errors with their generally dramatic effects on families and on communities. It is important to try to give as far as possible a scientifically based answer to this question. Fr. Haring, a moral theologian, citing scientific evidence finds it shocking that the rhythm method, so strongly and recently endorsed again by Church authorities, should be classified among the means of "birth control" by way of spontaneous abortion or at least by spontaneous loss of a large number of zygotes which, due to the concrete application of the rhythm method, lack of necessary vitality for survival. He goes on to state that the scientific research provides overwhelming evidence that the rhythm method in its traditional form is responsible for a disproportionate waste of zygotes and a disproportionate frequency of spontaneous abortions and a defective childern. Professor Hilgers, a reproductive physiologist, takes on opposite view, maintaining that the hypotheses are arbitrary and the alarm false. The strongest evidence upon which Fr. Haring bases his moral principles about the use of the natural methods of fertility regulation is a paper by Guerrero and Rojos (1975). These authors examined, retrospectively, the success of 965 pregnancies which occurred in women who were using the temperature method for family planning and who had recorded the menstrual day of insemination, and they concluded that their results suggested that aging of human spermatozoa in the female genital tract is associated with a increased frequency of spontaneous abortions and that postovulatory aging of human ova results in postimplatation. Their results and conclusions were accepted with great caution by the scientific community. The kind of evidence which suggests that the use of natural methods may increase, in particular cases, the loss of embryos or fetuses, stimulates further research, but it seems a very weak basis for the establishment of principles of human behavior. At the present stage of knowledge the natural methods for the regulation of fertility cannot be qualified as methods which necessarily and considerably increase the risks of abortion of malformed progeny.

A prospective multicentre trial of the ovulation method of natural family planning. I. The teaching phase

World Health Organization, 1981·Fertil Steril

The percentage of 869 women in five countries capable of being taught to recognize the periovulatory cervical mucus symptom of the fertile period was determined in a prospective multicentre trial of the ovulation method of natural family planning. The women were ovulating, of proven fertility, represented a spectrum of cultures and socioeconomic levels, and ranged from illiteracy to having postgraduate education. In the first of three standard teaching cycles, 93% recorded on interpretable ovulatory mucus pattern. Eighty-eight per cent of subjects successfully completed the teaching phase; 7% discontinued for reasons other than pregnancy, including 1.3% who failed to learn the method. Forty-five subjects (5%) became pregnant during the average 3.1-cycle teaching phase. The average number of days of abstinence required by the rules of the method was 17 in the third teaching cycle (58.2% of the average cycle length). To what extent the findings of this study can be extended to other couples remains to be demonstrated.

Possible involvement of endorphin withdrawal or imbalance in specific premenstrual syndromes and postpartum depression

Halbreich U et al., 1981·Medical Hypotheses

Breast cancer incidence in women with a history of progesterone deficiency

Cowan LD et al., 1981·Am J Epidemiol

In order to investigate the nature of the association of involuntarily delayed first birth and risk of breast cancer, 1083 white women who had been evaluated and treated for infertility from 1945-1965 were followed prospectively through April 1978 to ascertain their breast cancer incidence. These women were categorized as to the cause of infertility into two groups, those with endogenous progesterone deficiency (PD) and those with nonhormonal causes (NH). Women in the PD group had 5.4 times the risk of premenopausal breast cancer compared to women in the NH group. This excess risk could not be explained by differences between the two groups in ages at menarche or menopause, history of oral contraceptive use, history of benign breast disease or age at first birth. Women in the PD group also experienced a 10-fold increase in deaths from all malignant neoplasms compared to the NH group. The incidence of postmenopausal breast cancer did not differ significantly between the two groups.

Natural family planning III. Intermenstrual symptoms and estimated time of ovulation

Hilgers TW et al., 1981·Obstet Gynecol

Several periovulatory symptoms sometimes used in natural family planning are correlated with the estimated time of ovulation in 23 subjects and 64 hormonally normal menstrual cycles. The data suggest that intermenstrual pain may not be due to 1 specific cause but rather to several related factors. As a symptom of ovulation, intermenstrual pain was more specific than lower backache, abdominal bloating, and intermenstrual bleeding nonetheless, intermenstrual pain has a broad periovulatory association. The most reproducible and predictable sign of this series appeared to be the postovulatory occurrence of breast tenderness.

Puerperal Psychosis. Phenomena and diagnosis

Brockington IF et al., 1981·Arch Gen Psychiatry

Fifty-eight psychoses beginning within two weeks of childbirth are compared with 52 episodes of nonpuerperal psychotic illness occurring in young women. A clinical approach based on the use of multiple information sources and integrated assessment was used. Statistically significant differences between the two groups of patients were found in 52 of 214 psychopathological variables. Postpartum patients had more manic symptoms and "confusion," while nonpuerperal patients had more schizophrenic symptoms. The Research Diagnostic Criteria (RDC) showed an excess of schizoaffective (manic) puerperal patients and schizoaffective (depressed) or schizophrenic nonpuerperal patients. Only five of 58 puerperal episodes met RDC for schizophrenia. The relative lack of schizophrenic symptoms in the puerperal group was confirmed by self-ratings. The results are interpreted as supporting a link between puerperal psychosis and manic-depressive disease.

Sonographic monitoring of ovarian follicular development

Fleischer AC et al., 1981·J Clin Ultrasound

Serial sonographic examinations were performed on 15 volunteers five days during the expected midcycle. The 75 sonographic studies were evaluated in a nonbiased manner, and the following 1) the presence or absence of a follicle within the ovary; 2) if present, the average dimension of the follicle; 3) the ability to delineate both ovaries; and 4) the presence of associated changes, such as involution of the follicle, echogenic texture within the follicle, or fluid in the cul-de-sac. The sonographic findings were correlated with serial leutinizing hormone (LH) assays as well as basal body temperature charts. As defined in the study, the correlation between the sonographic findings and hormonal determination were considered excellent in 70% of the cases, good in 20%, and poor in 10%. Both ovaries were delineated in 73% of the examinations performed, thus substantiating the ability of sonography to detect maturing ovarian follicles.

Peritoneal fluid cell populations in infertility patients

Haney AF et al., 1981·Fertil Steril

Correlation of plasma gonadotrophins and ovarian steroids pattern with symptomatic changes in cervical mucus during the menstrual cycle in normal cycling women

Cortesi S et al., 1981·Contraception

27 healthy young Italian women were studied to evaluate their ability to identify symptomatically the potentially fertile phase of the menstrual cycle by self observation of their cervical mucus pattern as described in the Ovulation Method Billings. The women's observations were correlated with daily plasma levels of FSH, LH, estradiol-17 beta and progesterone. Ovulation was considered to occur on the day following the LH peak. The hormonal assays revealed that 2 of the 34 cycles studied were anovulatory. 24 of the 27 subjects in the study group demonstrated their ability to recognize the onset of the mucus discharge and the peak symptom from the first cycle after teaching, another two from the second cycle. The only other subject contributed an anovulatory cycle in which the hormonal assay confirmed the accuracy of her mucus observations. In the study, the mean interval between the time of ovulation as assessed and the peak symptom recorded by the subjects was 0.0 days, with a range from -2 to +1 days. The mean time interval from the first recorded symptom to the estimated day of ovulation was 6.0 days, with a range from 3 to 10 days. The study shows that young Italian women can be taught to recognize their cervical mucus pattern as described in the Ovulation Method Billings. The accuracy of their observations is demonstrated by the hormonal assays. The study also confirms the conclusion reached in earlier similar studies that there is a direct correlation between the cervical mucus symptom and the potentially fertile phase of the cycle. Research is currently being conducted on a larger number of couples employing the Ovulation Method Billings to actually regulate their fertility.

Successful treatment of polycystic ovary syndrome with spironolactone or bromocriptine

Blum I et al., 1981·Obstet Gynecol

Marked improvement in the severe hypertension (250/150 mmHg) and hirsutism of a patient suffering from polycystic ovary syndrome was quickly achieved by the use of spironolactone 200 mg per day. Substitution of spironolactone with bromocriptine induced further amelioration of these symptoms and renewal of ovulatory cycles. These drugs may afford another mode of therapy in patients with polycystic ovary syndrome.

Factors altering thyroid hormone metabolism

Robbins J, 1981·Environ Health Perspect

Thyroxine, the major secretory product of the thyroid gland, is metabolized in the peripheral tissues by phenolic conjugation, deamination, decarboxylation, and a cascade of monodeiodinations. This brief review focuses on the deiodination reactions, which currently are under intensive investigation. One product, 3,5,3'-triiodothyronine (T3), is the major active form of the thyroid hormone, and about 80% of the T3 produced in the body is derived extrathyroidally. Furthermore, a greater fraction of the T3 found on nuclear receptors in pituitary and brain cells is derived intracellularly, as compared to liver and kidney cells. The latter tissues, on the other hand, appear to be the source of most of the circulating T3. Another deiodinase, acting on the nonphenolic ring of T4, gives rise to the hormonally inactive 3,3',5'-triiodothyronine ("reverse" T3 or rT3). A number of physiological and pathological events perturb the deiodination pathway, leading to a decrease in T3 neogenesis and reciprocal changes in the circulating level of T3 (which decreases) and rT3 (which increases). This so-called "low T3 syndrome" is also produced by a number of pharmacological agents. The biological effects resulting from these changes are incompletely understood, but they are potentially important in the body's adjustment to stress and as a site of action of toxic agents. In addition, they are of obvious importance clinically because of their influence on serum T3 and TSH levels, which are commonly used tests of thyroid function.

Spontaneous abortion rate in patients with endometriosis

Naples JD et al., 1981·Obstetrics and gynecology

Intravaginal administration of progesterone: enhanced absorption after estrogen treatment

Villanueva B et al., 1981·Fertil Steril

A progesterone solution was administered by intravaginal instillation, intramuscular injection, and sublingually to estrogen-deficient women, with or without estradiol (E2) replacement, and serum progesterone (P) concentrations were measured by radioimmunoassay. Intravaginal application to postmenopausal subjects receiving E2 gave 10 times baseline at 15 minutes and 30 to 40 times at 1 to 2 hours, with sustained levels, for 7 hours and decline to 10 times baseline at 24 hours. Intravaginal application to hypoestrogenic women gave similar results, but of much lower magnitude (highest value, 20 times baseline). Intramuscular injection, in contradistinction, showed gradually increasing levels over the study period, up to 30 times basal values at 24 hours. It contrast, sublingual application produced very modest serum increases, to approximately 10 times baseline within 2 hours and return to basal value at 24 hours. Since the most rapid and highest levels were observed by vaginal application to postmenopausal women receiving estrogen, and considering that the vagina has been similarly shown to be very effective for estrogen absorption, it is conceived that full hormone replacement could be accomplished in the deficient states by cyclic vaginal application of both steroids.

Follicular phase treatment of luteal phase dysfunction

Hodgen GD et al., 1981·Fertil Steril

Previously, we demonstrated that selective suppression of serum follicle-stimulating hormone (FSH) in monkeys treated with charcoal-extracted porcine follicular fluid (pFF) in the early follicular phase induced luteal defects resembling those which occur spontaneously in women and monkeys. Here, we assessed whether luteal phase defects arising in association with induced FSH deficiencies during the early follicular phase can be treated by early FSH therapy. Rhesus monkeys were treated with pFF and human menopausal gonadotropin (hMG) (FSH:luteinizing hormone [LH], 3:1) on cycle days 1 to 3 or day 4, respectively. Daily femoral blood samples were analyzed for LH, FSH, and estradiol by radioimmunoassay. In the monkeys treated with the pFF-hMG combination, a single ovulation was uniformly noted at laparoscopy, and initial luteal phase elevations in serum progesterone levels were nearer those of normal ovulatory cycles than after pFF alone. These results suggest that FSH/LH treatment in the early follicular phase compensated, in part, for the pFF-induced deficiency in endogenous FSH levels.

Clinical investigation of the menstrual cycle. III. Clinical, endometrial, and endocrine aspects of luteal defect

Gautray JP et al., 1981·Fertil Steril

This study was intended to correlate different clinical and biologic parameters to better define luteal insufficiency (LI) and to contribute to a better understanding of its origin. Endometrial patterns were used as the basis for classification of clinical cases. Of 328 outpatients with menstrual disorders and/or infertility, 88 were considered to have LI. Their cycles were compared with 79 normal cycles. Two different principal endometrial pure LI, when the endometrium is more than 2 days out of phase; and LI with persistent estrogenic influence, when the histologic estrogenic stigmata are excessive during the luteal phase. Basal body temperature charts demonstrated either ovulation delay or a slow increase in temperature (longer than 2 days). Plasma steroid concentrations also demonstrated a perturbation progesterone levels were statistically significantly lower in LI than in normal cycles and this defect was worse when the estrogenic influence was persistent; the preovulatory estradiol peak was disturbed in all circumstances, as was the concentration of endometrial steroid receptors. These simultaneous abnormalities strongly suggest a central origin of LI.

Endogenous opiates modulate pulsatile luteinizing hormone release in humans

Ropert JF et al., 1981·J Clin Endocrinol Metab

To test the postulate that endogenous opioid peptides may be involved in the neuroendocrine mechanisms controlling the frequency and amplitude of LH pulses, saline and an opioid receptor antagonist, naloxone, were infused sequentially, each for 6-h intervals, in six normal cycling women during the luteal phase of the menstrual cycle. During naloxone infusion (1.6 mg/h), there was a significant (P less than 0.01) increase in both the frequency and amplitude of LH pulses compared to those in saline controls. FSH pulses were not discernible in individual subjects; however, a significant increment in FSH levels occurred concomitantly with the increase in LH. These data strongly suggest that endogenous opiates, through an inhibition of hypothalamic LRF, participate in the endocrine events leading to the low frequency of episodic LH secretion characteristic of the luteal phase of the human menstrual cycle.

Endorphins and the regulations of the human menstrual cycle

Blankstein J et al., 1981·Clin Endocrinol (Oxf)

In order to assess a possible influence of endogenous opioids upon gonadotrophin secretion in women, we examined the effects of i.v. administration of 10 mg naloxone, a specific opiate antagonist, in ten normal menstruating women, in thirteen women with amenorrhoea and/or hyperprolactinaemia and in two women with putative deficiency of gonadotrophin-releasing hormone (GnRH). In thirteen subjects, a saline vehicle control study (randomized order of administration) was also performed. In the normal women, naloxone failed to elicit changes in serum gonadotrophin levels when administered during the early follicular phase of the menstrual cycle. However, significant increments of LH were observed from 30 to 165 min following naloxone administration during the late follicular phase. Similar LH responses occurred in the amenorrhoeic and hyperprolactinaemic women. There was a tendency towards a concomitant increment in FSH levels, which reached statistical significance variably from 60 to 105 min post-naloxone. The LH response to naloxone in individual subjects showed a significant (P less than 0.01) quadratic (U-shaped) relationship to the log basal oestradiol concentration. No response to naloxone was observed in the two patients with GnRH deficiency despite a brisk response to an exogenous GnRH bolus. Taken together, these data suggest that central nervous system inhibitory opioid pathways may be involved in the regulation of LH secretion in normal women and that excessive production of endogenous opioids may play a role in the pathophysiology of some amenorrhoeic conditions.

The conservative surgical treatment of endometriosis: evaluation of pregnancy success with respect to the extent of disease as categorized using contemporary classification systems

Rock JA et al., 1981·Fertil Steril

A homogeneous group of 214 infertile women with endometriosis treated at the Johns Hopkins Hospital from 1960 to 1979 received conservative surgery as the sole therapeutic modality. Among this group, 115 patients (54%) conceived following surgery; of these conceptions, 109 resulted in a living child. Among 49 patients with secondary infertility, the spontaneous abortion rate was reduced from 49% to 20% after conservative surgery (P less than or equal to 0.01). Three contemporary classification systems were utilized to categorize patients according to the sites and amount of endometriosis at the time of conservative surgery. Those systems suggested by Buttram (Fertil Steril 30:240, 1978) and by Kistner and coauthors (Fertil Steril 28:108, 1977) revealed differences among fecundability rates among the different categories (P less than or equal to 0.01); however, the system suggested by The American Fertility Society (AFS) (Fertil Steril 32:633, 1979) revealed significant differences only if categories were combined (mild plus moderate versus severe plus extensive, P less than or equal to 0.05). Nevertheless, the AFS system revealed that pregnancy success was significantly reduced if an ovarian endometrioma was greater than 3 cm or had ruptured (P less than or equal to 0.01).

A fifteen year experience with ectopic pregnancy

Tancer ML et al., 1981·Surg Gynecol Obstet

The increasing importance of an ectopic pregnancy as a cause of maternal death presents a challenge that will be met when primary care physicians combine a high index of suspicion with the ability to recognize the patient most at risk. The major symptoms, abdominal pain, secondary amenorrhea and abnormal vaginal bleeding are well known, as are the major signs, abdominal tenderness, adnexal mass and tenderness on motion of the cervix. Less well known are factors in the clinical history which indicate the patient to be at high risk. These include primary or secondary infertility, previous abortion or ectopic pregnancy and previous tubal operation, either reconstructive or sterilizing. In addition, the use of an intrauterine contraceptive device or its recent removal because of abdominal pain or bleeding, or both, is highly significant. Of major importance is a history of recent uterine evacuation. Should the diagnosis of ectopic pregnancy be under consideration, procrastination by observation is no longer acceptable. An active effort must be made to confirm or deny the diagnosis, Culdocentesis should be performed in the emergency department or clinic. If positive, prompt laparotomy is indicated. Should the result of culdocentesis be unsatisfactory or negative, laparotomy should be undertaken with further delay.

The endocrinology of the opiates and opioid peptides

Morley JE, 1981·Metabolism

Since the isolation of the enkephalins five yr ago, there has been an explosive increase in knowledge concerning the effects of the opiates and opioid peptides. This review deals with the interactions of opiates with the endocrine system in rat and man. The opioid peptides have been demonstrated to exert a variety of effects on pituitary hormone secretion in rat and man. In the rat, opiates stimulate growth hormone, prolactin and ACTH release and inhibit the release of the glycoprotein hormones. In man, the physiologic role of the endogenous opiates appears to be involved predominantly in ACTH and gonadotrophin regulation. Opiate effects are mainly exerted at the level of the hypothalamus but further modulating effects may occur at the pituitary and at end-organs. Opiate-induced hormonal effects appear to be mediated through dopaminergic and/or serotonergic mechanisms. Recent studies have also suggested a possible local neuromodulatory role for the opioid peptides in the control of carbohydrate metabolism and reproductive processes.

Ovulation method of contraception

Billings JJ, 1981·Med J Aust

Overview of the biological aspects of the fertile period

France JT, 1981·Int J Fertil

The fertile period of the human menstrual cycle consists of those days on which sexual intercourse can result in a pregnancy. Its duration is determined by the functional life span of the gametes within the female reproductive tract. Various mechanisms control gamete transport and survival in the reproductive tract of the human female. The ovarian hormones estradiol and progesterone have an important role in regulating these mechanisms. The nature of cervical mucus and its governing influences on sperm transport and survival following coitus are of prime importance in defining the fertile days of the menstrual cycle. Man's early concepts of the fertile period were often based on erroneous theories of the female reproductive cycle. It is only since the late 1920's that a true understanding of ovulation and the menstrual cycle has evolved. Current approaches in natural family planning to recognizing the fertile and infertile days of the menstrual cycle are discussed and evaluated.

Ovulation and corpus luteum formation observed by ultrasonography

Nitschke-Dabelstein S et al., 1981·Ultrasound Med Biol

An epidemiologic study of preterm delivery

Berkowitz GS, 1981·Am J Epidemiol

A case-control study of the epidemiology of preterm delivery was undertaken at Yale-New Haven Hospital in Connecticut during 1977. The study population consisted of 175 mothers of singleton preterm infants and 313 mothers of singleton term infants. Significant risk factors of a preterm delivery included low socioeconomic status; low pregravid weight; inadequate weight gain during the pregnancy; a previous preterm delivery; a history of infertility problems; an induced abortion terminating the previous pregnancy; vaginal spotting or light bleeding during the pregnancy; antepartum hemorrhage and abnormal placental implantation; lack of leisure-time physical activities during the pregnancy; alcohol consumption prior to the third trimester of pregnancy; and negative attitudinal expression toward the pregnancy.

Effectiveness of the sympto-thermal method of natural family planning: an international study

Rice FJ et al., 1981·Int J Fertil

A 2-year international study involving NFP (natural family planning) associations in 5 countries (Canada Colombia France Mauritius U.S.) was conducted to evaluate statistically the effectiveness of the sympto-thermal method an NFP method which adds to the temperatiure method the observation of signs and symptoms of the ovulatory period. 1022 couples (21736 couples) were selected 1) the wife had to be between 19 and 44 years of age 2) the wife had to be of proven fertility by having carried a fetus for at least 28 weeks 3) the couple must have submitted 1 satisfactory temperature graphy before being accepted and 4) the couple must have expressed a willingness to submit temperature graphs for 2 years. 826 couples completed 24 months. Menstrual cycle length varied from 9 to 98 days with an average of 28.43 days. 205 women had a variation of 8 days or less. 128 unplanned pregnancies occured giving a rate of 7.47 conceptions/100 woman-years of exposure. Theoretical effectiveness was .93 pregnancies/100 woman-years using the Pearl Formula; 16 pregnancies occured in couples following instructions. Failure rate was 4.13% for couples trying to prevent pregnancies and 14.83% for couples only delaying a pregnancy. Failure rate of the method used alone was 7.16%; 8.19% used with other contraceptives. There was an average of 13 cycles per year per woman. Using the modified Pearl index (pregnancies per 1300 cycles rather than per 1200 months) the pregnancy rate was 7.66% vs. 7.47% for 1200 months. The study shows that the sympto-thermal method is effective and reliable. 2 1) whether a large group of people will accept a method that depends on periodic abstinence or 2) whether the method will be just as effective when used by couples who are not as well motivated as the participants in this study.

The effect of progesterone and progestogens on the foetus

Dalton K, 1981·Neuropharmacology

Cervical mucus: the biological marker of fertility and infertility

Billings JJ, 1981·Int J Fertil

The ovulation method provides a woman with an awareness of her cervical mucus pattern. This enables her to mark the beginning and end of the fertile phase of the cycle as well as the time of maximum fertility. Not only is the time of ovulation located but also there is recognition of infertility in the absence of ovulation. The key to understanding is the concept of the basic infertile pattern which precedes the commencement of follicular development; the key to successful use is competent teaching. After preliminary considerations on the fertile phase the determination of ovulation and the aspect of periodic abstinence two basic studies comparing clinical and hormonal observations are reviewed showing how accurately the cervical mucus reflects ovarian activity. Understanding the basic infertile pattern and the two sets of rules (the early day rules and peak rule identifying respectively the beginning and end of the fertile period) is basic to the application of the ovulation method. Criteria for the ideal family planning method and the importance of quality teaching are presented. Two problems requiring attention in NFP are restrictive terminology in data collection and a lack of fully developed and positive approach to periodic abstinence.

Presence of beta-endorphin-like immunoreactivity in the anterior pituitary gland of rat and man and evidence for the differential localization with ACTH

Watkins WB et al., 1981·Cell Tissue Res

Two antisera, Y-10 and Y-18 were raised in rabbits against synthetic human beta-endorphin conjugated to bovine serum albumin and keyhole limpet haemocyanin respectively. Antiserum Y-10 has been shown by radioimmunoassay to be highly specific for human beta-endorphin with minimal or no cross-reactivity against other pituitary peptides whilst antiserum Y-18 cross-reacted on an equimolar basis against beta-endorphin and beta-lipotropin. When used in the immunohistochemical procedure, both antisera specifically stained the corticotrophs in human anterior pituitary tissue. A similar effect was observed when antiserum Y-18 was applied to rat anterior pituitary tissue in the immunohistochemical procedure. Y-10 antiserum, on the other hand, stained not only rat corticotrophs but also somatotrophs. The somatotrophin staining could not be attributed to the enkephalins reported to be present in these cells. The non-specific beta-endorphin antiserum Y-18 was used to stain anterior pituitaries from dehydrated and adrenalectomized rats as well as rats of the Brattleboro strain. In tissues from the three experimental animals, cells that stained positively for beta-endorphin did not give a positive immunoreaction for ACTH and vice versa in some other sections. It is concluded that under the physiological conditions, formalin fixation of the tissue causes the pro-opiocortin molecule to be "trapped" in a conformation such that either ACTH or beta-endorphin-like determinants are available for reacting with the appropriate antiserum.

Correlations Between the Mucus Symptoms and the Hormonal Markers of Fertility Throughout Reproductive Life

Brown JB et al., 1981

Spontaneous abortion rate in patients with endometriosis

Naples JD et al., 1981·Obstet Gynecol

Congenital abnormalities and hormones during pregnancy: a clinical review

Schardein JL, 1980·Teratology

A review of the extensive literature on the subject indicates that sex hormones have been associated with a wide variety of adverse clinical conditions following usage during pregnancy. About 230 cases of female pseudohermaphroditism have been reported following use of hormones with androgenic potency, but masculinization observed with estrogens in a few females may represent only adrenal-stimulated pseudohermaphroditism. Feminization of males, mostly by progestogens in some 45 cases, is unproven at present. Realizing the limitations of the published studies when all present data are considered, there seems no justification for undue concern over the induction of nongenital congenital malformations through hormone use in pregnancy. The available data on the association to cardiac, limb, and CNS defects, and to several malformative syndromes, the effects appear to be remarkably nonspecific, the studies are contradicted by a large number of negative reports, and an increased incidence of defects with increased usage has not materialized. A possible exception are the CNS malformations associated with the use of the antifertility agent clomiphene, and careful surveillance is warranted at present. While a reasonable interpretation from this review would be that hormones present no major teratogenic hazard, elimination of hormonal exposure whenever possible during pregnancy is suggested.

Family Planning - "Billings" ovulation method

Bhering MS et al., 1980·Rev Esc Enferm USP

The authors present "Billing" ovulation method as natural family planning.

The treatment of pelvic inflammatory disease

Rees E, 1980·Am J Obstet Gynecol

The treatment of pelvic inflammatory disease depends upon the etiology of the condition. Pelvic infection (PI) after parturition and abortion, gynecologic surgery, and a variety of invasive procedures is commonly associated with the isolation of anaerobic and aerobic flora of the vagina. The factors which influence the choice of antimicrobial treatment and the role of Bacteroides fragilis and Escherichia coli are discussed. Sexually transmissible agents of importance are Neisseria gonorrhoeae and Chlamydia trachomatis. Pelvic infections associated with these pathogens require antibiotics which exert an optimum effect against them. Examination and treatment of the sexual partner(s) are important. The possible role of the anaerobic and aerobic vaginal flora as opportunistic secondary pathogens is discussed. Developments in the surgical treatment of the sequelae of PID are reviewed. The results of treatment of uncomplicated gonorrhea in 262 women are reported. C. trachomatis was isolated from 53% of women before treatment. After treatment, PI developed in 11 women who had been given penicillin and in one woman who had been given tetracycline (P = 0.0071). It is suggested that recognition and treatment of postgonococcal cervicitis in women treated for uncomplicated gonorrhea with penicillin might provide one form of preventive treatment for nongonococcal PI.

Ovum retention in the human

Craft I et al., 1980·Fertil Steril

Two cases of ovum retention occurring in postovulatory follicles are described. The ova were recovered at laparoscopy by aspiration of decompressed ovulatory follicles, one during a natural cycle and the other following a programmed clomiphene/human chorionic gonadotropin cycle. Each patient had a normal luteal phase with an increased progesterone level indicative of ovulation. The implications of these findings and their relevance to human fertility studies are discussed.